Misguided myeloid DC model of LCH pathogenesis. According to this model, the stage of differentiation in which pathologic ERK activation arises determines the clinical manifestations of LCH. In this model, activating mutations in hematopoietic stem cells or undifferentiated myeloid DC precursors result in multifocal high-risk disease, whereas mutations in tissue-restricted precursors results in multifocal low-risk disease, and mutations in more differentiated tissue-restricted precursor cells result in a single lesion. The CD207⁺ cells in LCH lesions represent differentiated myeloid cells with indistinguishable phenotype regardless of cell of origin that presumably recruit and activate other inflammatory cells.